Continuous Administration Of Propofol Research Articles

Propofol Decreases the Augmentation Index of Central Arteries via a Delay in the Pulse Wave Reflection

Background Procedural sedation with propofol is widely used to reduce stress and suppress cardiovascular responses to anxiety and fear during medical and dental treatments. A well-known adverse event of propofol is a decrease in peripheral vascular resistance resulting in hypotension; however, the effects on intravascular pressure at the central arteries are unknown. Intravascular pressure is formed by the synthesis of reflected waves from the periphery with forward pulse waves produced during ejection, and the augmented pressure by the reflected waves is one of the determinants of the systolic blood pressure (BP) at the central arteries and is known to be related to cardiovascular events. We tested the hypotheses that propofol reduces the augmentation index (AIx) in the carotid artery and that the reduction is caused by a delay in the arrival time of the reflected wave (Tr). Methods Beat-by-beat finger BP and heart rate (HR) were continuously recorded in seven healthy young men (Age: 30 ± 2 years). Central BP, AIx, Tr of the carotid artery, and carotid-to-femoral pulse wave velocity (cfPWV) were measured using applanation tonometry during supine rest before (BL) and 20 min after the onset of continuous administration of propofol (PRO). This study was approved by the Institutional Review Board of Matsumoto Dental University. Results Systolic BP was lower in PRO than in BL (P < 0.001) in both peripheral and central arteries, while it was lower in the central artery than in the peripheral artery in PRO (80 ± 5 and 96 ± 6 mmHg, P < 0.001). HR in PRO remained unchanged from BL. AIx was decreased (−40.9 ± 10.3 vs −11.8 ± 11.3%, P < 0.001), and Tr was prolonged (199 ± 14 vs 173 ± 8 ms, P < 0.001) in PRO than in BL at the carotid artery. A negative correlation was found between AIx and Tr (r = −0.91, P < 0.001). Furthermore, Tr was negatively correlated with cfPWV (r = −0.72, P = 0.004), but not with the effective reflected length (P = 0.291). Conclusions Since propofol delayed the time when the reflected wave reached the large vessels, the interval between the peaks of the forward wave and the reflected wave widened, resulting in a decreased peak value of the augmented pressure. These results suggest that the carotid artery pressure is decreased by propofol-induced reduction in augmentation pressure, which is dependent on the delay in the arrival time of the reflected wave to the central arteries.

Continuous Administration of Propofol Suppresses Osteoclast Differentiation of RAW264.7 Cells

Continuous Administration of Propofol Suppresses Osteoclast Differentiation of RAW264.7 Cells

Propofol-Associated Hypertriglyceridemia in Coronavirus Disease 2019 Versus Noncoronavirus Disease 2019 Acute Respiratory Distress Syndrome.

To characterize the incidence and characteristics of propofol-associated hypertriglyceridemia in coronavirus disease 2019 versus noncoronavirus disease 2019 acute respiratory distress syndrome. Single-center prospective, observational cohort study. Medical ICU and regional infectious containment unit. Patients with acute respiratory distress syndrome admitted from April 7, 2020, to May 15, 2020, requiring continuous propofol administration. None. Of 50 patients enrolled, 54% had coronavirus disease 2019 acute respiratory distress syndrome. Median Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were 35.5 (interquartile range, 30.2-41) and 8 (interquartile range, 6-9). Pao2/Fio2 ratio was 130.5 (interquartile range, 94.5-193.8). Patients with coronavirus disease 2019-associated acute respiratory distress syndrome experienced a higher rate of hypertriglyceridemia (triglyceride ≥ 500 mg/dL) than noncoronavirus disease 2019-associated acute respiratory distress syndrome (9 [33.3%] vs 1 [4.3%]; p = 0.014). Those with coronavirus disease 2019, compared with those without, received more propofol prior to becoming hypertriglyceridemic (median, 5,436.0 mg [interquartile range, 3,405.5-6,845.5 mg] vs 4,229.0 mg [interquartile range, 2,083.4-4,972.1 mg]; p = 0.027). After adjustment for propofol dose with logistic regression (odds ratio, 5.97; 95% CI, 1.16-59.57; p = 0.031) and propensity score matching (odds ratio, 8.64; 95% CI, 1.27-149.12; p = 0.025), there remained a significant difference in the development of hypertriglyceridemia between coronavirus disease 2019-associated acute respiratory distress syndrome and noncoronavirus disease 2019-associated acute respiratory distress syndrome. There was no difference between groups in time to hypertriglyceridemia (p = 0.063). Serum lipase was not different between those who did or did not develop hypertriglyceridemia (p = 0.545). No patients experienced signs or symptoms of pancreatitis. Patients with coronavirus disease 2019 acute respiratory distress syndrome experienced a higher rate of propofol-associated hypertriglyceridemia than noncoronavirus disease 2019 acute respiratory distress syndrome patients, even after accounting for differences in propofol administration.

Screening Protocol of Propofol Infusion Syndrome

Introduction: Propofol is often used as sedation for a long time in the ICU. The use is at risk of Propofol Infusion Syndrome (PRIS) which is characterized by arrhythmias or decreased heart function, metabolic acidosis, rhabdomyolysis, and acute renal failure. Literature Review: The pathophysiology of PRIS is due to a disturbance in cell metabolism which inhibits the transport of Free Fatty Acid (FFA) into cells and inhibits the mitochondrial respiration chain. The management of PRIS is supportive of every symptom that arises so that screening is needed as a treatment to reduce high mortality rates. Screening using creatine phosphokinase (CPK) and lactate is supporting data as an initial introduction for symptoms of PRIS. Conclusion: PRIS can occur if continuous administration of propofol &gt; 4 mg / kg / hour. CPK levels&gt; 5000 IU / L become a benchmark to stop propofol before the onset symptoms of PRIS. Implementation of screening protocol is very helpful for clinicians to reduce mortality in ICU due to the use of propofol.

Screening Protocol of Propofol Infusion Syndrome

Introduction: Propofol is often used as sedation for a long time in the ICU. The use is at risk of Propofol Infusion Syndrome (PRIS) which is characterized by arrhythmias or decreased heart function, metabolic acidosis, rhabdomyolysis, and acute renal failure. Literature Review: The pathophysiology of PRIS is due to a disturbance in cell metabolism which inhibits the transport of Free Fatty Acid (FFA) into cells and inhibits the mitochondrial respiration chain. The management of PRIS is supportive of every symptom that arises so that screening is needed as a treatment to reduce high mortality rates. Screening using creatine phosphokinase (CPK) and lactate is supporting data as an initial introduction for symptoms of PRIS. Conclusion: PRIS can occur if continuous administration of propofol &gt; 4 mg / kg / hour. CPK levels&gt; 5000 IU / L become a benchmark to stop propofol before the onset symptoms of PRIS. Implementation of screening protocol is very helpful for clinicians to reduce mortality in ICU due to the use of propofol.

A Nasal High-Flow System Prevents Hypoxia in Dental Patients Under Intravenous Sedation

Hypoxia is a major complication in dental patients under intravenous sedation (IVS). A nasal high-flow (NHF) system has been reported to achieve effective oxygenation in patients with sleep apnea syndrome. This study investigated the ability of the NHF system to prevent hypoxia in dental patients under IVS. Thirty patients scheduled for dental treatment under IVS were enrolled. Patients were randomly divided into 3 groups: patients spontaneously breathing oxygen at 5L/minute through a nasal cannula (NC5 group), patients administered oxygen at 30L/minute through the NHF system, and patients administered oxygen at 50L/minute through the NHF system. Hypnosis was induced by bolus administration of midazolam (0.05mg/kg) followed by continuous administration of propofol (target blood concentration, 1.2 to 2μg/mL). Noninvasive blood pressure, peripheral capillary oxygen saturation (SpO2), heart rate, and bispectral index values were recorded every 2.5minutes before the induction of anesthesia. Interventions, such as jaw lifting, were recorded during IVS and arterial blood gas analysis was performed at the end of sedation. Patient and surgeon satisfaction with IVS was evaluated by interview. Minimum SpO2 was lowest in and surgeons were least satisfied with the NC5 group. In addition, interventions were required most frequently in the NC5 group (P < .05). Compared with the NC5 group, use of the NHF system improved partial pressures of oxygen and carbon dioxide in dental patients under IVS (P < .05). These results suggest that use of the NHF system can prevent hypoxia in dental patients under IVS. Further studies are necessary to determine the appropriate flow rate and indications for NHF in obese patients.

Cough Reflex Under Intravenous Sedation During Dental Implant Surgery Is More Frequent During Procedures in the Maxillary Anterior Region

The present study was performed to evaluate the incidence of cough episodes and the association between cough episodes and patient-related and site-specific parameters during implant surgery when performed under intravenous sedation. One hundred forty-seven patients scheduled for dental implant surgeries under intravenous sedation were enrolled in this study. Heart rate, blood pressure, percutaneous oxygen saturation, and bispectral index were monitored. Sedation was induced intravenously by a bolus administration of midazolam and maintained by a continuous administration of propofol. Sedation level was adjusted to achieve scores of 3 to 4 on the Ramsay Sedation Scale. Surgical procedures were divided into 11 stages. Implant sites were labeled as right maxillary molar, maxillary anterior, left maxillary molar, right mandibular molar, mandibular anterior, and left mandibular molar sites. When coughing occurred, heart rate, blood pressure, percutaneous oxygen saturation, bispectral index, procedure being performed, and surgical site being stimulated were recorded. One hundred seventy-two cough episodes were observed in 97 patients (66%). Cough episodes occurred during all stages of surgery but were substantially more frequent during preparation of the implant site. The incidence of cough episodes was significantly higher at the maxillary anterior site and lowest at the right mandibular molar areas. These findings suggest that difficulties in swallowing and in the suction of intraoral fluids have variable effects at different surgical sites. Careful suction of intraoral water and an appropriate sedation level are required, especially in procedures in the maxillary anterior region.

Stepwise sedation for elderly patients with mild/moderate COPD during upper gastrointestinal endoscopy.

To investigate stepwise sedation for elderly patients with mild/moderate chronic obstructive pulmonary disease (COPD) during upper gastrointestinal (GI) endoscopy. Eighty-six elderly patients with mild/moderate COPD and 82 elderly patients without COPD scheduled for upper GI endoscopy were randomly assigned to receive one of the following two sedation methods: stepwise sedation involving three-stage administration of propofol combined with midazolam [COPD with stepwise sedation (group Cs), and non-COPD with stepwise sedation (group Ns)] or continuous sedation involving continuous administration of propofol combined with midazolam [COPD with continuous sedation (group Cc), and non-COPD with continuous sedation (group Nc)]. Saturation of peripheral oxygen (SpO2), blood pressure, and pulse rate were monitored, and patient discomfort, adverse events, drugs dosage, and recovery time were recorded. All endoscopies were completed successfully. The occurrences of hypoxemia in groups Cs, Cc, Ns, and Nc were 4 (9.3%), 12 (27.9%), 3 (7.3%), and 5 (12.2%), respectively. The occurrence of hypoxemia in group Cs was significantly lower than that in group Cc (P < 0.05). The average decreases in value of SpO2, systolic blood pressure, and diastolic blood pressure in group Cs were significantly lower than those in group Cc. Additionally, propofol dosage and overall rate of adverse events in group Cs were lower than those in group Cc. Finally, the recovery time in group Cs was significantly shorter than that in group Cc, and that in group Ns was significantly shorter than that in group Nc (P < 0.001). The stepwise sedation method is effective and safer than the continuous sedation method for elderly patients with mild/moderate COPD during upper GI endoscopy.

Inter-individual variability in propofol pharmacokinetics in preterm and term neonates

To document covariates which contribute to inter-individual variability in propofol pharmacokinetics in preterm and term neonates. Population pharmacokinetics were estimated (non-linear mixed effect modelling) based on the arterial blood samples collected in (pre)term neonates after i.v. bolus administration of propofol (3 mg kg(-1), 10 s). Covariate analysis included postmenstrual age (PMA), postnatal age (PNA), gestational age, weight, and serum creatinine. Two hundred and thirty-five arterial concentration-time points were collected in 25 neonates. Median weight was 2930 (range 680-4030) g, PMA 38 (27-43) weeks, and PNA 8 (1-25) days. In a three-compartment model, PMA was the most predictive covariate for clearance (P<0.001) when parameterized as [CL(std).(PMA/38)(11.5)]. Standardized propofol clearance (CL(std)) at 38 weeks PMA was 0.029 litre min(-1). The addition of a fixed value in neonates with a PNA of >/=10 days further improved the model (P<0.001) and resulted in the equation [CL(std).(PMA/38)(11.5) +0.03] for neonates >/=10 days. Values for central volume (1.32 litre), peripheral volume 1 (15.4 litre), and peripheral volume 2 (1.29 litre) were not significantly influenced by any of the covariates (P>0.001). PMA and PNA contribute to the inter-individual variability of propofol clearance with very fast maturation of clearance in neonatal life. This implicates that preterm neonates and neonates in the first week of postnatal life are at an increased risk for accumulation during either intermittent bolus or continuous administration of propofol.

Propofolinfusionssyndrom

The propofol infusion syndrome is a rare but potentially lethal complication resulting from a prolonged continuous administration of propofol. It was first described in the beginning of the 1990's and in recent years there have been frequent reports of problems in association with the use of propofol sedation. The cardinal signs and symptoms of the propofol infusion syndrome are metabolic acidosis, rhabdomyolysis, renal failure, cardiac arrhythmias and a progressive, often therapy-resistant cardiac failure. The pathophysiology of this syndrome appears to involve a disturbance of mitochondrial metabolism induced by propofol. Our report involves a case of propofol infusion syndrome in a patient having undergone cardiac surgery.

Diazepam and propofol used as anesthetics during open-heart surgery do not cause chromosomal aberrations in peripheral blood lymphocytes

Diazepam is a benzodiazepine with anticonvulsant, anxiolytic, sedative and muscle-relaxing properties. Many aspects of its toxicity have been investigated, including genotoxic and carcinogenic effects in various model systems. However, it is still unclear whether diazepam is in fact a genotoxic agent. Propofol is a rapid-onset, short-acting intravenous anesthetic agent. It is used widely for the induction and maintenance of anesthesia as well as for long-term sedation in intensive care units. There is limited information in the literature on its genotoxic effects. Both drugs are commonly used as anesthetic in patients undergoing open-heart surgery. Therefore, we investigated the possible genotoxic effects of propofol and diazepam in those patients, using a chromosomal aberration (CA) assay. Peripheral blood samples were collected from 45 patients before induction of anesthesia and at the end of the anesthesia with diazepam or propofol. In Group I ( n = 24), anesthesia was induced with 0.2 mg kg −1 diazepam and 10 μg kg −1 fentanyl. In Group II ( n = 21), anesthesia was induced with 1 mg kg −1 propofol and 10 μg kg −1 fentanyl. Pancuronium bromide (0.1 mg kg −1) was administered for skeletal muscle relaxation in both groups. Anesthesia was maintained by diazepam administration at 5 mg kg −1 in Group I or by continuous propofol administration at 2–4 mg (kg h) −1 in Group II. All patients received 0.02 mg kg −1 pancuronium and 5 μg kg −1 fentanyl boluses at 30–40 min intervals for anesthesia maintenance. Body temperature was controlled during bypass in the two groups. We found that the mean frequency of CAs in both groups before and at the end of the anesthesia were not statistically significantly different. Our analysis also indicated that age, smoking habit and gender were not confounding factors. In conclusion, our results indicate that diazepam and propofol do not exert genotoxic effects in blood cells during open-heart surgery.

Propofol

Patients in the ICU who require intubation and mechanical ventilation benefit from adequate sedation and analgesia. Traditionally, this has been achieved using benzodiazepines and opioids. Alternatively, propofol is being administered for sedation of patients in the ICU with increasing frequency. Propofol has a number of properties that make it a potentially superior choice for sedation of intubated ICU patients. The rapid onset and offset of sedation with propofol, even after prolonged administration, allow for greater control over the level of sedation and more rapid weaning from mechanical ventilation. In addition, long-term administration of propofol does not appear to be associated with the development of tolerance, addiction, or withdrawal following discontinuation. Propofol suppresses cellular oxygen consumption and carbon dioxide production without increasing anaerobic metabolism. This may be beneficial in patients with severe hypoxemia, hypercarbia, or myocardial ischemia. Finally, the use of propofol may reduce or eliminate the need for other medications in these patients such as muscle relaxants, antihypertensives, lipid nutritional supplements, and analgesics, thereby simplifying their medication regimens and reducing the overall cost of their care while in the ICU. Propofol can be administered to critically ill patients for sedation with a high degree of safety and efficacy. Propofol causes systemic vasodilatation which may result in unwanted hypotension, especially in patients who are already hemodynamically compromised. Propofol also causes ventilatory depression, so its use should be restricted in the ICU to patients whose airway is protected by an endotracheal tube and whose ventilation is closely monitored. Finally, continuous administration of propofol may cause clinically significant hypertriglyceridemia in patients with disordered triglyceride metabolism, or in patients receiving excessive doses of propofol or parenteral lipid supplements. Although propofol is more expensive than equipotent doses of other sedative agents, the additional cost of using propofol for sedation of critically ill patients in the ICU may be more than offset by the savings accrued from faster times to extubation, shorter ICU stays, and the use of fewer medications to manage these patients. Further research needs to be done to determine the potential clinical and cost benefits of using propofol for sedation of patients in the ICU.

Induction and maintenance of propofol anaesthesia. A manual infusion scheme.

A simple, manually controlled infusion scheme for continuous administration of propofol was derived by simulation of a computer algorithm designed to achieve a predetermined blood concentration of propofol within 2 minutes and to maintain a constant blood level for the duration of surgery. The manual infusion scheme for a target blood propofol concentration of 3 micrograms/ml, consisted of a loading dose of 1 mg/kg followed immediately by an infusion of 10 mg/kg/hour for 10 minutes, 8 mg/kg/hour for the next 10 minutes and 6 mg/kg/hour thereafter. An overall mean blood propofol concentration of 3.67 micrograms/ml was achieved within 2 minutes and maintained stable for the subsequent 80-90 minutes of surgery. The decrease of systolic and diastolic arterial pressures at induction was much less than that previously described after larger induction doses of propofol and there was a negligible haemodynamic response to laryngoscopy and intubation or to the subsequent surgery. The quality of induction and maintenance of anaesthesia was satisfactory in every patient.